Affective illness tends to remit and recur spontaneously and with increasing frequency. Its course is also characterized by a tendency for manic episodes to be immediately preceded or followed by depressive episodes, with no intervening normal period, and for mania to alternate with depression. In rapid cycling affective disorder these tendencies are so pronounced that mania and depression recur regularly and frequently with a continuous, circular course. Rapid cycling cases comprise about 15% of patients in lithium or affective disorder clinics, and they are difficult to treat. The purpose of this project was to gain further insights into the causes and treatments of rapid cycling affective disorder by comparing data obtained from rapid cycling and non-rapid cycling patients with regard to their clinical features and course of illness. All rapid cycling patients admitted to our research program since 1973 were included in the study. For comparison, a non-rapid cycling control group was also investigated. Information regarding the patients' psychiatric and medical histories, family histories, cause of illness, and responses to treatments was derived from hospital charts, research flow charts containing records of prospective daily mood ratings, treatments and procedures, and structured follow-up interviews. We found that 1) rapid cycling affective disorder is phenotypically and genetically related to more typical forms of bipolar affective disorder; 2) there was a high prevalence of thyroid disease during lithium treatment in both rapid cycling and non-rapid cycling women; 3) although nearly all the rapid cycling patients were women, there was no convincing evidence that the rapid cycles were generated by the menstrual cycle; 4) treatment with antidepressant drugs was associated with reversible rapid cycling in approximately 50% of the rapid cycling patients; patients experienced sowing or cessation of cycling when the drugs were withdrawn. The observation that antidepressants may have been responsible for rapid cycling in half the cases has obvious implications for prevention and treatment of rapid cycling, and it provides a clue to possible neurochemical causes of rapid cycling.